Volume 16 Supplement 1

24th Annual Computational Neuroscience Meeting: CNS*2015

Open Access

Model-based prediction of maximum pool size in the ribbon synapse

  • Caitlyn M Parmelee1Email author,
  • Matthew Van Hook2,
  • Wallace B Thoreson2, 3 and
  • Carina Curto4
BMC Neuroscience201516(Suppl 1):P41

https://doi.org/10.1186/1471-2202-16-S1-P41

Published: 18 December 2015

The synaptic ribbon is a specialized structure in photoreceptor neurons that tethers vesicles prior to release (Figure 1A). When a cell is stimulated, vesicles are released from the ribbon and later replenished from the population of mobile vesicles in the synaptic terminal. A train of depolarizing pulses causes the ribbon to alternate between periods of release (lasting Δt = 25 ms) and replenishment (lasting T = 50ms), which occur on estimated timescales of τr = 5 ms (for release) and τa = 815 ms (for replenishment). After the first few pulses, the system approaches a limit cycle, and the amount of vesicles released on each pulse converges to a limiting value, R (Figure 1B). This can be used to determine the maximum available pool size on the ribbon, A. The standard method for estimating A is to measure the rate of replenishment in the limit, and then back-extrapolate from the cumulative release plot to obtain the available pool size at the start of the pulse train [1]. When comparing pulse trains of different strengths, this method yields substantially different values for A, a somewhat paradoxical result. Back-extrapolation assumes, however, that the replenishment rate is constant, even though it is thought to be proportional to the available space on the ribbon [2].
Table 1

Maximum pool size predictions from pulse train data

Stimulus

Estimate for A, from back-extrapolation

Estimate for A, from the model

-10 mV (stronger)

-136.8794 pA

-131.6858 pA

-30 mV (weaker)

-75.1020 pA

-133.6100 pA

Figure 1

A) The synaptic ribbon. (B) The available pool size, A(t), during a stimulus pulse train.

We developed a model-based approach to estimate A from the limiting release R. We modeled the rate of release (resp. replenishment) to simply be proportional to the number of vesicles on the ribbon (resp. vacant ribbon sites), and using the measured timescale τr (resp. τa). By solving the alternating differential equations, we derived a recurrence relation for the release during each pulse, Ri, which we then solved to obtain a closed form expression for Ri and the limiting release R. Specifically, we found that A = cR, where c is a function of τra,Δt,T, and p, with p a release constant that captures the stimulus dependence of release probabilities, and can be estimated from the first release, R1. In contrast to the back-extrapolation method, our model-based estimate for A was similar across stimulus types (Table 1), while p was much smaller for the weaker stimulus. This suggests that available pool size does not change with stimulus strength; instead, differences in release result from changes in release probability.

Authors’ Affiliations

(1)
Department of Mathematics, University of Nebraska-Lincoln
(2)
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center
(3)
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
(4)
Department of Mathematics, The Pennsylvania State University

References

  1. Sakaba T, Schneggenburger R, Neher E: Estimation of quantal parameters at the calyx of Held synapse. Neurosci Res. 2002, 44 (4): 343-356.PubMedView ArticleGoogle Scholar
  2. Van Hook MJ, Parmelee CM, Chen M, Cork KM, Curto C, Thoreson WB: Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors. J Gen Physiol. 2014, 144 (5): 357-378.PubMedPubMed CentralView ArticleGoogle Scholar

Copyright

© Parmelee et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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